Dataset Information

Brief Report: HIV-1 Infection Impairs CD16 and CD35 Mediated Opsonophagocytosis of Mycobacterium tuberculosis by Human Neutrophils.

ABSTRACT: Using a flow cytometric assay, we investigated neutrophil-Mycobacterium tuberculosis opsonophagocytosis and the impact of HIV-1-infected serum on this process. The mean (±SD) percentage of neutrophils internalizing bacilli after 30 minutes incubation was significantly reduced by pretreatment with anti-CD16 (18.2% ± 8.1%, P < 0.001) or anti-CD35 antibody (23.2% ± 10.6%, P < 0.05) versus anti-CD4 controls (29.9% ± 8.1%). Blocking CD88 or CD11a did not affect internalization. Using heat-inactivated serum, maximal internalization was lower using HIV-1-infected serum versus HIV-1-uninfected. Using non-heat-inactivated serum, internalization decreased more rapidly with sequential dilutions of HIV-1-infected versus HIV-1-uninfected serum. CD16 and CD35 are important for neutrophil internalization of M. tuberculosis, whereas HIV-1 infection adversely affects opsonophagocytosis.

SUBMITTER: Bangani N

PROVIDER: S-EPMC5018214 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Brief Report: HIV-1 Infection Impairs CD16 and CD35 Mediated Opsonophagocytosis of Mycobacterium tuberculosis by Human Neutrophils.

Bangani Nonzwakazi N Nakiwala Justine J Martineau Adrian R AR Wilkinson Robert J RJ Wilkinson Katalin A KA Lowe David M DM

Journal of acquired immune deficiency syndromes (1999) 20161101 3

Using a flow cytometric assay, we investigated neutrophil-Mycobacterium tuberculosis opsonophagocytosis and the impact of HIV-1-infected serum on this process. The mean (±SD) percentage of neutrophils internalizing bacilli after 30 minutes incubation was significantly reduced by pretreatment with anti-CD16 (18.2% ± 8.1%, P < 0.001) or anti-CD35 antibody (23.2% ± 10.6%, P < 0.05) versus anti-CD4 controls (29.9% ± 8.1%). Blocking CD88 or CD11a did not affect internalization. Using heat-inactivated ...[more]

PMID: 27258232

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Project description:The bacterial pathogen Staphylococcus aureus responds to the host environment by increasing the thickness of its cell wall. However, the impact of cell wall thickening on susceptibility to host defenses is unclear. Using bacteria incubated in human serum, we show that host-induced increases in cell wall thickness led to a reduction in the exposure of bound antibody and complement and a corresponding reduction in phagocytosis and killing by neutrophils. The exposure of opsonins bound to protein antigens or lipoteichoic acid (LTA) was most significantly reduced, while opsonization by IgG against wall teichoic acid or peptidoglycan was largely unaffected. Partial digestion of accumulated cell wall using the enzyme lysostaphin restored opsonin exposure and promoted phagocytosis and killing. Concordantly, the antibiotic fosfomycin inhibited cell wall remodeling and maintained the full susceptibility of S. aureus to opsonophagocytic killing by neutrophils. These findings reveal that host-induced changes to the S. aureus cell wall reduce the ability of the immune system to detect and kill this pathogen through reduced exposure of protein- and LTA-bound opsonins.ImportanceUnderstanding how bacteria adapt to the host environment is critical in determining fundamental mechanisms of immune evasion, pathogenesis, and the identification of targets for new therapeutic approaches. Previous work demonstrated that Staphylococcus aureus remodels its cell envelope in response to host factors and we hypothesized that this may affect recognition by antibodies and thus killing by immune cells. As expected, incubation of S. aureus in human serum resulted in rapid binding of antibodies. However, as bacteria adapted to the serum, the increase in cell wall thickness resulted in a significant reduction in exposure of bound antibodies. This reduced antibody exposure, in turn, led to reduced killing by human neutrophils. Importantly, while antibodies bound to some cell surface structures became obscured, this was not the case for those bound to wall teichoic acid, which may have important implications for vaccine design.

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Dataset Information

Brief Report: HIV-1 Infection Impairs CD16 and CD35 Mediated Opsonophagocytosis of Mycobacterium tuberculosis by Human Neutrophils.

Publications

Brief Report: HIV-1 Infection Impairs CD16 and CD35 Mediated Opsonophagocytosis of Mycobacterium tuberculosis by Human Neutrophils.

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